Hypotensive activities of 11 synthetic derivatives of platelet activating factor (PAF) were examined and compared with their activities to produce endothelium-related relaxation of isolated rat thoracic aorta. The derivatives showed variety of hypotensive activities; some of the derivatives were more potent than natural PAF and some were virtually inactive compared to PAF. However, all of the compounds tested exhibited exactly the same activities to produce endothelium-related vasodilation. These results confirmed our previous view that the PAF-induced hypotension is not solely due to the endothelium-related vascular relaxation observed in vitro.